Conus regius-Derived Conotoxins: Novel Therapeutic Opportunities from a Marine Organism

Conus regius is a marine venomous mollusk of the Conus genus that captures its prey by injecting a rich cocktail of bioactive disulfide bond rich peptides called conotoxins. These peptides selectively target a broad range of ion channels, membrane receptors, transporters, and enzymes, making them valuable pharmacological tools and potential drug leads. C. regius-derived conotoxins are particularly attractive due to their marked potency and selectivity against specific nicotinic acetylcholine receptor subtypes, whose signalling is involved in pain, cognitive disorders, drug addiction, and cancer. However, the species-specific differences in sensitivity and the low stability and bioavailability of these conotoxins limit their clinical development as novel therapeutic agents for these disorders. Here, we give an overview of the main pharmacological features of the C. regius-derived conotoxins described so far, focusing on the molecular mechanisms underlying their potential therapeutic effects. Additionally, we describe adoptable chemical engineering solutions to improve their pharmacological properties for future potential clinical translation.     

Ethnicity and conflict: theory and facts

Over the second half of the 20th century, conflicts within national boundaries became increasingly dominant. One-third of all countries experienced civil conflict. Many (if not most) such conflicts involved violence along ethnic lines. On the basis of recent theoretical and empirical research, we provide evidence that preexisting ethnic divisions do influence social conflict. Our analysis also points to particular channels of influence. Specifically, we show that two different measures of ethnic division--polarization and fractionalization--jointly influence conflict, the former more so when the winners enjoy a "public" prize (such as political power or religious hegemony), the latter more so when the prize is "private" (such as looted resources, government subsidies, or infrastructures). The available data appear to strongly support existing theories of intergroup conflict. Our argument also provides indirect evidence that ethnic conflicts are likely to be instrumental, rather than driven by primordial hatreds.     

Characterization of Pectobacterium brasiliense strains from potato and vegetables in Israel

Pectobacterium brasiliense (Pbr) infects a wide range of crops worldwide, causing potato blackleg and soft rot and vegetable soft rots. This study aimed to characterize the genetic diversity and virulence variability among 68 Pbr strains isolated from either symptomless potato progeny tubers, diseased potato plants, ware potatoes wash water, or vegetables grown in Israel, as well as strains isolated from symptomless seed tubers grown in Europe, or diseased potato plants grown in France. The collection was typed using PCR and TaqMan real-time PCR analyses, dnaX sequence analysis, pulsed-field gel electrophoresis (PFGE), and pectolytic activity. dnaX phylogeny grouped almost all strains in a common genetic clade related to Pbr, which was distinct from the other Pectobacterium species. PFGE analysis identified two main clusters, including one major group of 47 strains with 95%–100% similarity. Maceration assays on two potato cultivars showed significant differences between strains but with no correlations with the source of the strains nor the status of the host (with/without symptoms). Molecular (dnaX sequences and PFGE profiles) and phenotypic analyses (tuber maceration tests) showed that the tested Pbr strains are not a homogeneous group. Analysis of the tested Pbr strains isolated from potato and vegetables grown in fields with a history of potato cultivation suggests that seed tubers imported from Europe may be the main source for Pbr in Israel. To the best of our knowledge, this is the first study that describes biodiversity and population structure of P. brasiliense isolated from potato and vegetables under hot climate conditions.     

Sex reversal and growth performance in juvenile females of the freshwater crayfish <Emphasis Type="Italic">Cherax quadricarinatus</Emphasis> (Parastacidae): effect of increasing temperature and androgenic gland extract in the diet

Monosex male culture of C. quadricarinatus is proposed for increasing yields because males reach a larger size at harvest than females. An experiment was done to evaluate the effects of androgenic gland extract and temperature on sex reversal and somatic growth in early juvenile females. Females were exposed to the following experimental conditions: C: control food and temperature maintained at 26 ± 1°C; HT (high temperature): control food and temperature maintained at 28.5 ± 1°C; VHT (very high temperature): control food and temperature maintained at 31 ± 1°C; AG: food with enriched with androgenic gland (1/10 dose for each juvenile per day) and temperature maintained at (26 ± 1)°C. The juveniles were weighed, sexed, and growth increment (GI) and growth rate (GR) were calculated twice a month. The HT and AG groups differed from the C group in GI and GR indicating a greater somatic growth. At the end of the experiment, the HT and AG groups had similar weight but only the HT group had enhanced oocyte diameter, with some vitellogenic oocytes compared to the C group. In the HT group, there was significant sex reversal, as indicated by development of male and intersex male characteristics in different individuals. Both temperature and AG diet have a high potential for culture of this species because of their enhancement of somatic growth; higher temperature increases the proportion of males, a desirable characteristic of cultured populations.     

Experimental infection of turkeys with avian pneumovirus and either Newcastle disease virus or Escherichia coli

Avian pneumoviruses (APVs) are RNA viruses responsible for upper respiratory disease in poultry. Experimental infections are typically less severe than those observed in field cases. Previous studies with APV and Escherichia coli suggest this discrepancy is due to secondary agents. Field observations indicate APV infections are more severe with concurrent infection by Newcastle disease virus (NDV). In the current study, we examined the role of lentogenic NDV in the APV disease process. Two-week-old commercial turkey poults were infected with the Colorado strain of APV. Three days later, these poults received an additional inoculation of either NDV or E. coli. Dual infection of APV with either NDV or E. coli resulted in increased morbidity rates, with poults receiving APV/NDV having the highest morbidity rates and displaying lesions of swollen infraorbital sinuses. These lesions were not present in the single APV, NDV, or E coli groups. These results demonstrate that coinfection with APV and NDV can result in clinical signs and lesions similar to those in field outbreaks of APV.     

Spontaneous gastroduodenal perforation in 16 dogs and seven cats (1982-1999)

The records of 23 dogs and cats diagnosed with spontaneous gastroduodenal perforation (GDP) were retrospectively reviewed. Survival was 63% in dogs and 14% in cats. Rottweilers <5 years of age were overrepresented. Clinical evidence of gastrointestinal bleeding was common in dogs but not in cats. Shock was an uncommon presenting condition in dogs and was not closely linked to outcome. In fact, progression of an ulcerating lesion to GDP was not associated with marked changes in symptoms exhibited by many patients in this study. Most GDPs were associated with histopathological evidence of subacute or chronic peritoneal reaction at the time of diagnosis. This suggests that diagnostic methods employed lacked sensitivity in identifying early perforating lesions, and that dramatic signs of acute abdomen following gastroduodenal perforation may not be as common as was previously thought.     

Quantitative study of 'flame follicles' in skin sections of Shar-pei dogs

This study determined the frequency of occurrence and the mean number of 'flame follicles' per skin section and assessed their diagnostic significance in cutaneous biopsies of Shar-pei dogs. The number of 'flame follicles' per section was recorded in skin sections from 42 Shar-pei dogs, of which 40 had non-neoplastic skin disease and non-atrophic dermatoses and 2 had healthy skin. Forty-two skin sections from dogs of different breeds served as control specimens, 28 of which were examples of non-neoplastic and non-atrophic dermatoses and 14 were from dogs with healthy skin. Differences among groups were analysed by means of the unpaired Student's t-test. It was concluded that 'flame follicles' were more frequent and found in significantly higher numbers in the Shar-pei group when compared with the control group suggesting that 'flame follicles' in skin sections from Shar-pei dogs do not have the same diagnostic significance as in other breeds.